Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Isavuconazonium Sulfate in Healthy Adult Japanese Subjects.

Abstract

Isavuconazonium sulfate is the water‐soluble prodrug of the novel, broad‐spectrum, triazole antifungal agent isavuconazole. This was a first‐in‐Japanese study assessing the pharmacokinetics, safety, and tolerability of isavuconazonium sulfate. The study was conducted in 2 parts: part 1 (single ascending dose; 100‐, 200‐, and 400‐mg equivalent of isavuconazole oral or intravenous administration); and part 2 (multiple doses for 16 days; 200‐mg equivalent of isavuconazole oral or intravenous administration; once‐daily administration with a loading regimen every 8 hours for the first 48 hours). A total of 60 and 16 subjects were randomized in part 1 and part 2, respectively. Observed clearance was lower in this study compared to what was previously reported in predominantly White populations and similar to clearance in non‐Japanese Asian populations. The range of the plasma isavuconazole concentration in this study was within the range of the pivotal phase 3 study, with no relationship between isavuconazole exposure and either efficacy or safety. There were no serious adverse events, and all reported treatment‐emergent adverse events were of mild intensity. This study confirmed that isavuconazonium sulfate was safe and well tolerated in healthy adult Japanese subjects.